Basic derivatives of substituted cycloalkanecarboxylic acids and methods of preparing same



Patented Aug. 31, 1954 UNITED STATES PATENT OFFICE BASIC DERIVATIVES OF SUBSTITUTED CYCLOALKANECARBOXYLIC ACIDS AND METHODS OF PREPARING SAME William A. Lott, Maplewood, and John Krapcho, New Brunswick, N. J., assignors to Mathieson Chemical Corporation, New York, N. Y., a corporation of Virginia No Drawing. Application February 12, 1952, Serial No. 271,272

13 Claims. 1

wherein R--CO is the acyl residue of a carboxylic acid,

RII

represents an amino group, n represents .one of the whole numbers 2 to 5 inclusive, and X is a member of the class consisting of O, NH, N(a1kyl), and N(aryl) groups; (B) acid-addition salts of (A); (C) quaternary ammonium salts of (A) and (D) methods of preparing (A), (B) and (C). [In the acyl residue RCO, the radical R may, for example, be an aliphatic, aromatic, alicyclic, or heterocyclic group; and it may be unsubstituted or may contain substituents such as alkyl, aikoxy, hydroxy and halogen groups] Among the preferred compounds of this invention are; basic esters having the following general formula Y aryl-C 0 C O O--0 (lower alkylenc)N (CH9 Z wherein represents a member of the class consisting of (lower alkyl) (lower alkyl) l-piperidyl, l-pyrrolidyl and 4-morpholinyl, and n has the meaning given hereinbefore; the acidaddition salts thereof; and the quaternary ammonium salts thereof with alkyl halides.

These compounds are useful and advantageous therapeutic agents, especially antispasmod'ics. Thus, the hydrochloride of 2-diethylami1'ioethyl 'l -benzoylcyclopropanecarboxylate, a compound representative of group B defined hereinbefore,

2 may be administered in the same general manner (e. g. orally, in tablet form) for the same general purpose is. g. for reduction of rigidity in Parkinsons disease) and with the same general results as the hydrochloride of B-diethylaminoethyl 1-phenylcyclopentanecarboxylate, an antispasmodic widely used and accepted by the medical profession. Addiitonally, these compounds (especially the quaternary ammonium salts, such as the methobromide of 2-diethylaminoethyl 1-benzoylcyclopropanecarboxylate) exhibit antisecretory efiects, and hence are useful in the treatment of gastric ulcers, for example.

Basic esters of the general formula:

wherein r is one of the whole numbers 2 and 3, are prepared by the method which essentially comprises interacting the corresponding acid (I) which may be in salt, (especially alkali-metal salt) form, with a basic aliphatic halide (II) of the general formula:

RI (halogen)(alkylene)-N \RII in an organic solvent for the reactants, removing the solvent and recovering the residue. The reaction occurs in the presence or absence of an alkaline condensing agent. Thus the following acids I and basic aliphatic halides II, inter alia, may be used for the preparation of the basic esters of this invention.

1-benzoylcyclopropanecarboxylic acid 1-benzoylcyclobutanecarboxylic acid 1-sorboylcyclopropanecarboxylic acid 1-nicotinoylcyclopropanecarboxylic acid l-cinnamoylcyclopropanecarboxylic acid 1- (Z-furoyl) -cyclopropanecarboxylic .acid 1-hexahydrobenzoylcyclopropanecarboxylic acid 1- (a-naphthoyl) -cyclopropanecarboxylic acid l-iz-thenoyl) -cyclopropanecarboxylic acid 1--(2-thenoyl) -cyclobutanecarboxylic acid 1 (2-methylpropanoyl) -cyelopropanecarboxylic acid l-anisoylcyclopropanecarboxylic acid l-anisoylcyclobutanecarboxylic acid l-propenoylcyclopropanecarboxylic acid l-acetylcyclopropanecarboxylic acid 2-diethylaminoethyl chloride 3-diethylaminopropyl chloride 3- l-piperidyl) -propyl chloride- 2-(1-pyrrolidyl) -ethyl chloride 2- (l-morpholinyl) -ethy1 chloride 3-diethylamino-2,2-dimethylpropyl chloride 2- l-piperidyl) -ethyl chloride 2-diethylamino-l-ethyl-ethyl chloride 2-diethylaminoisopropyl chloride [The acid reactants I are described in the literature, or are prepared as described hereinafter from compounds described in copendingapplication Serial No. 271,273 filed of even date] While basic esters in which the cycloalkyl group is cyclopentyl or cyclohexyl can be prepared by the method described hereinbefore, they are preferably prepared by the method described hereinafter. The method essentially comprises interacting a base (III) of. the general formula:

wherein s is one of the whole numbers 4 to 5 inclusive, with an acyl halide (IV) of .the general formula RCO(halogen) in the presence of an alkaline condensing agent and in an inert organic solvent for the reactants.

Thus the following bases III and acyl halides IV, inter alia, may be used in the practice of this invention:

3-dimethylaminopropyl cyclohexanecarboxylate 2- l-piperidyl) -ethyl cyclohexanecarboxylate 2- (4-morpholinyl) -ethyl cyclohexanecarboxylate 2 diethylamino 1 ethyl ethyl cyclohexanecarboxylate h H I Z-diethylaminoethyl cyclopentanecarboxylate 2-diethylaminoethyl cyclohexanecarboxylate 2- (l-piperidyl) -isopropyl cyclopentanecarboxylate 2-diethylaminoisopropyl cyclohexanecarboxylate 2- (1-pyrrolidy1) -ethyl cyclohexanecarboxylate 3-diethylamino 2,2-dimethylpropyl cyclohexanecarboxylate [These basic esters may be obtained conveniently by reacting the appropriate cycloalkane carbonyl halide with the appropriate aminoaliphatic-alcohol (cf Example 9 hereinafter).]

Sorboyl chloride Cinnamoyl chloride Nicotinoyl chloride Benzoyl bromide u-Naphthoyl'chloride s-Naphthoyl chloride Anisoyl chloride Propenoyl chloride Z-thenoyl chloride Z-methylpropanoyl bromide Hexahydrobenzoyl chloride Furoyl chloride The alkaline condensing agents utilizable for the purposesof this invention comprise, inter alia, sodamide, lithium amide, sodium ethoxide, potassium t-butoxide, (metallic) alkali metals, such as sodium and potassium, (solid) alkali metal hydroxides, such as NaOH and KOH, and (preferably) alkali metal derivatives of triphenylmethane. Preferably the alkaline condensing agent is dissolved or suspended in an inert organic solvent (especially ether) and this solution (or suspension) is used as the reaction medium.

TheJcasic amides of this invention are obtained by interacting an ester (V) of the general formula:

RCO/-C-C OO-(lower alkyl) wherein R and n have the meaning given hereinbefore with an alkylene diamine (VI) having a free amino hydrogen. Thus the following reactants V and VI are utilizable in the practice of this invention.

Ethyl 1-benzoylcyclopropanecarboxylate Methyl 1-benzoylcyclobutanecarboxylate Ethyl 1-benzoylcyclopentanecarboxylate Ethyl 1-benzoylcyclohexanecarboxylate Ethyl 1- (Z-thenoyl) -cyclopropanecarboxylate Ethyl 1-acetylcyclopropanecarboxylate Ethyl 1-furoylcyc1opropanecarboxylate [These esters may be obtained conveniently by reacting an ester of the appropriate cycloalkanecarboxylic acid with the appropriate acyl halide IV, or by the method described in copending application Serial No. 271,273 filed of even date] N ,N-dimethyl-N -ethyl-ethylenediamine N,N-diethyl-N'-methyl-ethy1enediamine N ,N- diethyl-butylenediamine N,N-diethyl-pentylenediamine N,N dimethyl N phenyl ethylenediamine [JACS 68, 1999 (1946)] N,N-diethylethylenediamine N (2-amino-ethyl) -piperidine N- (2-amino-ethyl) -pyrrolidine N,N-dimethyl-propylenediamine N- (2-amino-ethyl) -morpholine N,N-diethyl-isopropylenediamine In these methods, the bases may be obtained as such (1. e., as the free base) or in the form of their acid-addition salts (e. g., as hydrochlorides, if the halogen in the reactant is chlorine). The acid-addition salts may be converted to the free bases in the conventional manner, i. e., by neutralization with alkali; and the free bases may be converted to other acid-addition salts by reacting the base with the desired acid in a suitable solvent. The utilizable acids comprise, inter alia: hydrobromic, boric, nitric, lactic, tartaric, citric, succinic, phosphoric, sulfuric, maleic, fumaric and (especially) hydrochloric.

By the addition of alkyl halides, dialkyl sulfates, aralkyl halides, aryl halides, or the like, there are obtained in the usual manner quarternary ammonium salts of the basic esters and amides (A) described hereinbefore.

The following example are illustrative of the invention.

EXAMPLE 1 Preparation of Z-dz'ethylaminoethyl l-benzoylcyclopropanecarboxylcte hydrochloride EXAMPLE 2 Preparation of Z-(I-piperidyD-ethyl .1-benzoylcyclopropanecarboazylate, and the hydrochloride thereof A suspension of sodium isopropoxide, prepared from 8.3 gsodium and300 ml. isopropyl alcohol, is cooled and treated with 34.2 g, l-benzoylcyclopropanecarboxylic acid, followed by the addition of 33.1 g. 2-(1-pi'peridyl) -ethyl chloride hydrochloride. The resulting mixture is stirred and refluxed for 22 hours, the solvent is removed by distillation under reduced pressure, and the residue is treated with 50 ml. water. The mixture is then extracted with 400 ml. ether and the extract dried over magnesiumsulf'ate. After evaporation of the solvent, the residue is fractionated to yield about 45.5 g. of the base, a colorless oil which distills at about l61-168 C. at 0.2 mm. Part of this material (23.1 g.) is dissolved in 300 ml. dry ether and the solution is treated with a slight excess of ethereal hydrogen chloride, to yield a-colorless precipitate (the hydrochlorideof the base) weighing about 25.1 g., and melting at about 135-136 C. After two crystallizations from butanone, the crystalline product melts at about 137-138 C.

EXAMPLE 3 Preparation of Z-aimethyZaminoethg Z l-benzoylcyclopropanecarboxylate, and the hydrochlo ride thereof A solution of 4.23 g. sodium in 350 ml. isopropyl alcohol is treated with 35.0 g. 1--benzoylcyclopropanecarboxylic acid, followed by addition of a solution of about 24.0 g. Z-dimethylaminoethyl chloride in 150 ml. of toluene. This mixture is refluxed for two hours and the product, the free base, i isolated in the manner-described in Example 2; yield about 32.6 g. B. P. about 133-l36 C./0.5 mm. Part of this base (21.5 g.) is dissolved in 50 ml. of absolute alcohol and treated with one equivalent of alcoholic hydrogen chloride. Dilution of this solution with ether yields a colorless precipitate, the hydrochloride, weighing about 24.0 g. M. P. about 131-133 C. After crystallization from isopropyl alcohol, the crystalline product melts at about 134-l35 C.

EXAMPLE 4 Preparation of Z-dipropylaminoethyl I-benzoylcyclopropaneoarbomylate, and the hydrochloride thereof A solution of 2.88 g. sodium in 400 ml. isopropyl alcohol is treated with 23.8 g. l-benzoylcyclopropanecarboxylic acid, followed by addition of 20.4 g. 2-dipropylaminoethyl chloride. The mixture is refluxed for two hours and the product, the free base,is isolated in the manner described in :Example 2; yield about 26.5 g. B. P. about EXAMPLE 5 Preparation of 2-(4-morpholz'nyl) ethyl I-beneoylcyclopropanecarborcylate, and the hydrochlortdethereof A solution of 4.56 g. of sodium in 350 ml. isopr'opyl alcohol is treated with 37.7 g. l-benzoylcyclopropanecarboxylic acid, followed by addition of 31.5 g. 2-(4-morpholinyl) ethyl chloride. This mixture is refluxed for three hours and the product, the free base, is isolated in the manner described in Example 2-; yield about 50.0 g. B. P.

' about 167-169 C./0.2 mm. Part of thisbase (30.8 g.) is dissolved in m1. of absolute alcohol and treated with one equivalent of alcoholic hydrogen chloride. Dilution of this solution-'"with ether yields a crystalline precipitate, the hydrochloride, weighing about 34.0 g., M. P. about 143-l44 C. The product crystallizes from isopropyl alcohol, M. P. about 143-144 C EXAMPLE 6 Preparation of 3-dimethg Zaminoproq fl/Z 1-bemzoylcyclopropanecarboxylate, and they hydrochloride thereof A solution of sodium isopropylate, prepared from 4.23 g. of sodium and 350 ml. isopropyl alcohol, is treated with 35.0 g. l-benzoylcyclopropanecarboxylic acid, followed by addition of 22.4 g. '3- dimethylaminopropyl chloride. The mixture is refluxed for two hours and the product, the free base, i isolated in the manner described inExample 2; yield about 38.6 g., B. P. about -l38 C./0.3 mm. Part of this base (25.5 g.) is dissolved in 50 ml. absolute alcohol and treated with one equivalent of alcoholic hydrogen chloride. Dilution of this solution with ether yields a crystalline product, the hydrochloride, weighing about 26.5 g., M. P. about 144-l46 C. After recrystallization from isopropyl alcohol, the crystalline material melts at about -146" 0.

EXAMPLE 7 Preparation of Z-diethylamirvoethyl Z-(Z-thenoyZ) -cyclopropaneoarborylate, and the hydrochloride thereof 66, 1768 (1944)] and 54.5 g. ethylene bromide;

and the mixture is refluxed for six hours. After cooling, the mixture is treated with a solution of 5.0 g. sodium in 100ml. ethanol and the material is then refluxed for five hours, cooled andtdiluted with 500 ml. water. The resulting solution is extracted with ether and the ethereal phase Washed several times with Water until the aqueous phase is neutral. The ether phase is dried over magnesium sulfate, filtered and solvent evaporated. Distillation of the residue yields about 23.8 g. of the ester, ethyl 1-(2-thenoyl)- cyclopropane carboxylate; B. P. about 127-130 C./4 mm.; n :l.5434.

(1)) Part of the above ester (22.9 g.) is added to a solution of 23 g. of potassium hydroxide in 300 ml. of 95% alcohol and the resulting solution refluxed for two hours. After cooling, the mixture is diluted with 500 ml. of water and then extracted several times with ether. The aqueous phase is acidified with dilute sulfuric acid and the resulting liberated acid extracted with ether. After drying over magnesium sulfate, the solvent is evaporated and the residue crystallized as long blade-like crystals. This material is suspended in hexane and filtered; yield about 12 g., M. P. about 135-138 C. After crystallization from 50% alcohol, the 1-(2-thenoyl)cyclopropanecarboxylic acid weighs about 9.5 g., M. P. about 139- 141 C. (with evolution of a gas).

(0) A solution of 0.94-g. sodium in ml. iso- 7 propyl alcohol is treated with 8.0 g. 1-(2-thenoyl) cyclopropanecarboxylic acid, followed by the addition of 6.8 2-diethylaminoethyl chloride. The mixture is refluxed for three hours and the product, the free base, is isolated in the manner described in Example 2; yield about 9.6 g., B. P. about 146-148" C./0.5 mm. This material is dissolved in 50 ml. absolute alcohol and treated with one equivalent of alcoholic hydrogen chloride. Dilution of this solution with ether produces a crystalline product weighing about 10.8 g., M. P. about 136-137 C. After crystallization from butanone, this hydrochloride melts at 137-138 C.

EXAMPLE 8 Preparation of 2-diethylamz'noethyl I-benzoylcyclobutanecarborylate and the hydrochloride thereof (a) 1-benzoylcyclobutanecarbozcylic acid-A solution of 12.36 g. l-(a-hydroxybenzyl)cyclobutanecarboxylic acid, prepared for example as described in my copending application Serial No. 271,273 filed of even date, in 60 ml. 1 N sodium hydroxide is diluted with 100 ml. water and then treated dropwise over a period of one hour with a solutionf 6.32 g. potassium permanganate in 300 ml. water. After stirring for an additional two hours at room temperature, the purple-colored mixture is slowly warmed to 70 C. at which point it becomes colorless. The material is cooled, treated with charcoal, filtered, and the filtrate acidified with dilute sulfuric acid. The colorless crystalline product which separates is filtered and washed with water. This acid is dissolved in a small quantity of ether and precipitated by the addition of hexane to yield about 6.2 g. of product melting at 98 C. (with evolution of a gas). After crystallization from a mixture of benzene and hexane, the crystalline acid melts at about 103 C. (with evolution of a gas).

(1)) 5.7 g. 1-benzoylcyclobutanecarboxylic acid, prepared in (a) above, is added to a cool solution of 0.65 g. sodium in 150 ml. isopropyl alcohol and the resulting slurry i then treated with 3.9 g. 2-diethylaminoethyl chloride. This mixture is refluxed for four hours, cooled and the solvent removed by distillation under reduced pressure. The residue is treated with 25 ml. water, the product extracted with ether and the resulting ethereal solution dried over magnesium sulfate. After evaporation of the solvent, the residue is fractionated to yield about 5.2 g. of the free base, B. P. about 148-151 C./0.3 mm. One gram of the distillate is dissolved in 20 ml. ether and treated with a slight excess of ethereal hydrogen chloride to yield a colorless precipitate, the hydrochloride which when purified by crystallization from butanone melts at about 135-136 C.

EXAMPLE 9 Preparation of Z-diethylaminoethyl I-beneoylcyclopentanecarboccylate and the hydrochloride thereof (a) Z-dzethylaminoethyl cyclopentanecarboa:- yZate.A cooled solution of 38.5 g. of cyclopentanecarbonyl chloride [Perkin, J. Chem. Soc. 65, 99 (1884)] in 150 ml. dry benzene is treated dropwise (30 minutes) with a solution of 34.0 g. 2-diethylaminoethanol in 100 ml. of dry benzene; a colorless precipitate separating. After stirring for 1 hour at room temperature, the mixture is refluxed for 2 hours, cooled, and extracted with 250 ml. of water. The aqueous phase is then washed with 100 ml. ether and treated with a 8 cooled solution of 16.0 g. of sodium hydroxide in ml. water; and the liberated base is extracted with 300 ml. ether and dried over magnesium sulfate. After evaporation of the ether, the residue is fractionated to yield about 44 g. of colorless product, boiling at about 96-98 C./2 mm.

(b) 19.4 g. 2-diethylaminoethyl cyclopentanecarboxylate is added to 650 ml. of 0.14 M. ethereal solution of triphenylmethylsodium [J A. C. S. 63, 3156 (41)], the mixture is stirred for 2 hours at room temperature, and 13.0 g. benzoyl chloride is added over a period of 15 minutes. After allowing the mixture to stand overnight, it is refluxed for 2 hours, cooled, and 100 ml. water is added. The aqueous layer is discarded, and the ether layer is extracted first with 8.5 ml. concentrated hydrochloric acid in 100 ml. water and then with 50 ml. water. These aqueous extracts are combined, made alkaline with a solution of 5.0 g. sodium hydroxide in 25 ml. water, and extracted with 300 ml. ether to yield the free base. The latter is dried over magnesium sulfate and the solvent is evaporated; and the residue is dissolved in 400 ml. dry ether and treated with a slight excess of ethereal hydrogen chloride, to yield about 32 g. of a colorless precipitate (the hydrochloride of the free base), melting at about 121-123 C. After 2 crystallizations from butanone, the product melts at about 127-128 C.

EXAMPLE 10 Preparation of Z-diethylaminoethyl I-Denzoglcyclohemanecarboaylate and the hydrochloride thereof 650 ml. of a 0.14 M. ethereal solution of triphenylmethylsodium is treated with 20.5 g. 2-diethylaminoethyl cyclohexanecarboxylate [B. P. 98-l00 C. at 2 mm., prepared from the hydrochloride described in Chem. Abstracts 43, 1023 (1949) l and then with 12.6 g. benzoyl chloride, as described in Example 9b, yielding a crude residue (the base) weighing about 32 g.

18 g. of this crude residue is dissolved in 300 ml. ether and treated with a slight excess of ethereal hydrogen chloride, yielding about 18.5 g. of precipitate (the hydrochloride of the base),

melting at about 130-135 C. After 2 crystallizations from butanone, the product melts at about -141" C.

EXAMPLE 11 Preparation of Z-diethylaminozsopropyl l-berbeoylcyclohercanecarborg/late hydrochloride (a) Z-dz'ethylaminoisopropyl cyclohexanecarboccylate.A solution of 60.0 g. cyclohexanecarbonyl chloride [Ber. 30, 1941 (1897)] in 200 ml. dry benzene is treated with a solution of 53.6 g. 2-diethylaminoisopropanol in 150 m1. dry benzene, as described in Example 9a, yielding about 89.5 g. of the basic ester, distilling at about 100-101 C. (2 mm.).

(b) Interaction (as described in Example 91)) of 650 ml. of a 0.14 M. ethereal solution of triphenylmethylsodium with 22 g. 2-diethylaminoisopropyl cyclohexanecarboxylate, prepared as described in (a), above, followed by 13.0 g. benzoyl chloride, yields about 32.2 g. 2-diethylaminoisopropyl 1 benzoylcyclohexanecarboxylate hydrochloride. This crude product melts at about l37-l39 C.; and after recrystallization from 150 ml. butanone, it melts at about 144- 145 C.

Preparation of Z-diethylaminoethyl I-(Z-thenoyl)cyclohemanecarboxylate and the hydrochloride thereof tals melt at.about.168-169.C. and are the-hyr drochloride of the base.

EXAMPLE 13 Preparation of 3-dimethylami'noprop'yl I-bensoyZcycloheaanecarboxylate and the hydror chloride thereof (a) 3-dimethylaminopropyl cyclohea'anecarboayZate.--A solution of 60.0 g. of cyclohexanecarbonyl chloride in 200 ml. dry benzene is treated with a solution of 42.4 g. of 3-dimethylaminopropanol in 150 ml. dry benzene. The free base, isolated according to the procedure described in Example 9a, weighs about 68.0 'g.'and boils. at about 99-101 C. at 3 mm.

(b) A mixture of 650 ml. of, an ethereal 0.15 M. solution of triphenylmethylsodium, 21.4 g gdimethylaminopropyl cyclhexanecairbo$cylate and 15.4 g. benzoyl chloride is reacted accord ing to the procedure described in Example 9b. The colorless crude base (about 33 g.) is dissolved in 400 ml. ether and treated with a slight excess of ethereal hydrogen chloride, to yield about 35.0 g. of a colorless precipitate (the hydrochloride of the base) which is purified by crystallization from butanone; melting at about 98-101 C.

EXAMPLE 14 Preparation of N-(2-diethylaminoethyl)1-benzoylcyclopropcmeoarboramide hydrochloride 21.8 g. of ethyl 1benzoylcyclopropanecarboxylate [J. Chem. Soc. 4'7, 836 (1885)] and 11.6 g. Z-diethylaminoethylamine are mixed and heated at 100 C. for about 6 hours. The reaction mixture is dissolved in 50 ml. absolute ethanol, and a slight excess of alcoholic hydrogen chloride is added. Dilution with 500 ml. dry ether precipitates the product, which is purified by crystallization from butanone.

Using methyl 1-benzoylcyclobutanecarboxylate, prepared as described in copending application Serial No. 271,273 filed of even date, in place of the corresponding cyclopropane ester in this example, N (2 diethylaminoethyD-lbenzoylcyclobutanecarboxamide hydrochloride is obtained.

EXAMPLE Preparation of a quaternary ammonium salt (the methobromide) of Z-diethylaminoethyl 1 beneoylcycloprop anecarboarylate A solution of 11.9 g. z-diethylaminoethyl 1- benzoylcyclopropanecarboxylate (prepared from the hydrochloride as described in Example 1) in 10 m1. of acetone is treated with a solution of 7.6 g. methyl bromide in 50 ml. acetone; and the solid which precipitates is filtered off and dried,

yielding about 150 .g.'of the product, melting at about 132-134 C. After recrystallization from butanol the colorless product weighs about 9.5 g., and melts at about 145" C.

Using molar equivalents of ethyl bromide, benzylchloride, dimethyl sulfate, or methyl ptoluene-sulfonate in place of methylbromide in this example the corresponding quaternary ammonium salts of 2-diethylaminoethyl l-benzoylcyolopropanecarboxylate are prepared.

Using molar equivalents of the free basesxprepared in Examples 3, 4, 5 and 6 in place of. 2- dimethylaminoethyl 1, 7 benzoylcyclopropanecarboxylate in this example; the following quater nary ammonium salts respectively are prepared: the methobromide of 2-dimethylaminoethyl 1- benzoylcyclopropanecarboxylate M. P. about 1 66-166 C. (after crystallization from absolute alcohol M. P. about 168-1'70 0.); the methobromide of 2-dipropylaminoethyl l-benzoylcyclopropanecarboxylate M. P; about 120 C. (after several recrystallizations from butanoneether M. P. about 12 1-125" C1); the methobromide of 2-(4-morpholinyl) ethyl l-b'enzoylcyclopropanecarboxylate M. P. about 155-157 C. (after crystallization from absolute alcohol M. P. about. 157-159 C.); the methobromide of 3 dimethylaminopropyl 1 benzoylcyclopropanecarboxylate crystallized from isopropyl alcohol M. P. about -136? C.

EXAMPLE 16 Preparation of a quaternary ammonium salt (the methobromide) of Z-diethylaminoethyl 1 beneocyclohexanecarboxylate A. solution of 6.8 g. Z-diethylaminoethyl 1- benzoylcyclohexanecarboxylate (prepared as described in Example 10) "in 10' ml. of acetone is treated with a solution of 3.0 g. methyl bromide in 75 ml. acetone. The resulting colorless precipitate is filtered off and crystallized from 200 ml. acetone; it weighs about 6.1 g., and melts at about -152 C. After recrystallization from butanone, the colorless product melts at about l51l53 C.

The invention is variously otherwise embodied within the scope of the appended claims.

We claim:

1. A compound of the class consisting of: bases of the general formula wherein R is a member of the class consisting of phenyl and thienyl, X represents a member of the class consisting of O and NH, and

represents a member of the class consisting of )lower alkyl) N (lower alkyl) l-piperidyl, 1-pyrrolidyl, and -morpholinyl; acid-addition salts thereof; and quaternary ammonium salts thereof.

2. An acid-addition salt of a base of the general formula:

(lower alkyl) phenyl- C OCC O O(lower alkylene) N HZCCH2 (lower alkyl) 8. A quaternary ammonium salt of a base of the general formula:

5. A quaternary ammonium salt of a base of the general formula:

(lower alkyl) C CC O O-(lower alkylene)-N I S H: C.-QH: (lower alkyl) 6. 2diethylamin0ethyl l-benzoylcyolopropanecarboxylate hydrochloride.

7. 2 dimethylaminoethyl l benzoylcyclopro panecarboxylate hydrochloride.

8. 2-diethylaminoethyl 1-(2-thenoyl) -cyclopropanecarboxylate hydrochloride.

9. The methobromide of 2-diethy1aminoethyl 1- benzoylcyclopropanecarboxylate.

10. The methobromide of 3-dimethylaminopropyl 1-benzoylcyclopropanecarboxylate.

11. A base of the general formula:

(lower alkyl) phenyl-C 0-0-0 0 0- (lower alkylene)-N H:CCH:

12. A base of the general formula:

(lower alkyl) (lower alkyl) 12 13. The method which essentially comprises interacting wherein R is a member of the class consisting of phenyl and thienyl groups, with a basic aliphatic halide of the general formula Y (ha1ogen)(lower a1kylene)-N wherein represents a member or the class consisting of (lower alkyl) (lower alkyl) 1 piperidyl, l pyrrolidyl, and 4 morpholinyl groups, in an organic solvent for the reactants, removing the solvent and recovering the residue.

References Cited in the file of this patent UNITED STATES PATENTS Number Name Date 2,561,385 Leonard July 24, 1951 2,573,015 Hafiiger et a1 Oct. 30, 1951 OTHER REFERENCES Tilford et al.: J. Am. Chem. Soc., vol. 69, pp. 2902-6, 1947. 

1. A COMPOUND OF THE CLASS CONSISTING OF: BASES OF THE GENERAL FORMYLA 